Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy

Abstract

This report summarizes the recommendations of the multiple system atrophy (MSA) Working Group on Diagnostic Neuropathology Criteria for MSA that was part of an international MSA Workshop held on 26 and 27 April 2007 in Boston, MA. The workshop was supported by a grant from the National Institute of Neurological Disorders and Stroke that was intended to convene a group of international experts to revise and update criteria for the clinical and neuropathological diagnosis of MSA. The MSA Workshop recognized the glial cytoplasmic inclusions (GCIs) composed of filamentous alpha-synuclein as a defining morphological feature of MSA, and it recommends that widespread GCIs should be a criterion for the definite neuropathological diagnosis of MSA. The deliberations and recommendations of the Working Group on Diagnostic Neuropathology Criteria for MSA are summarized in this report.

Second consensus statement on the diagnosis of multiple system atrophy

“…The first, definite MSA, requires the neuropathologic findings of widespread and abundant CNS ␣-synuclein-positive glial cytoplasmic inclusions (Papp-Lantos inclusions) in association with neurodegenerative changes in striatonigral or olivopontocerebellar structures. 15 Criteria for probable MSA are listed in table 1 and for possible MSA are listed in tables 2 and 3. 3 Patients with predominantly parkinsonian features should continue to be designated MSA-P, and patients with predominantly cerebellar ataxia should be designated MSA-C. We appreciate that the predominant motor feature can change with time; thus, patients who present with cerebellar ataxia can develop increasingly severe parkinsonian features until these latter features dominate the clinical presentation.…”

“…DISCUSSION On clinical presentation, MSA appears with a combination of autonomic failure with parkinsonism or cerebellar ataxia or both, and the previous criteria and the present criteria recognize this fundamental feature of the disease. The current criteria also retain the distinctions between levels of diagnostic certainty, using the term definite MSA for subjects with autopsy demonstration of typical histologic features, 15 probable MSA for patients with autonomic failure plus parkinsonism or cerebellar ataxia, and possible MSA for people with clinical findings that do not as yet clearly represent this disease.…”

Glial cytoplasmic inclusions in neurologically normal elderly: prodromal multiple system atrophy?

“…MSA has neuronal loss and gliosis in the substantia nigra, posterior putamen, inferior olive, pontine nuclei and cerebellum with pathognomonic α-synuclein immunoreactive glial cytoplasmic inclusions (GCI) [21,25]. It is unknown to what extent GCI are present in clinically normal individuals.…”

Dopamine cell loss in the periaqueductal gray in multiple system atrophy and Lewy body dementia

“…All patients had signed informed consent for autopsy according to the Institutional Review Board guidelines. Twelve cases (9 men, 3 women, age 61 Ϯ 3 years) had clinical and neuropathologically proven MSA according to current criteria 14,15 ; 12 cases (11 men, 1 woman, age 79 Ϯ 4 years) had clinical diagnosis of DLB and neuropathologic neocortical or limbic stage Lewy body disease (LBD) 16 ; and 12 control cases (7 men, 5 women, ages 67 Ϯ 4 years) had no history of neurologic disease. As a group, the DLB cases were older ( p Ͻ 0.01) than the control and MSA cases; there was no significant age difference between MSA and control cases.…”

“…The neuropathologic diagnosis of MSA or LBD was made according to current consensus criteria. 15,16 The presence of neurofibrillary tangles and senile plaques was classified in each case according to the stages of Alzheimer disease (AD) as described by Braak and Braak (B&B) 18 and defined by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). 19 Of the 12 MSA cases, 10 had severe involvement of the putamen and substantia nigra pars compacta and 6 had moder- Age is given in years.…”